Ketoacids? Good medicine?
Ketoacids? Good medicine?
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DOI：
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发表时间：
2003
影响因子：
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通讯作者：
G. Cahill;R. Veech
中科院分区：
文献类型：
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作者：
G. Cahill;R. Veech
D-β-羟基丁酸，饥饿的人的主要“酮”体，取代葡萄糖作为大脑的主要燃料，减少肝脏（和肾脏）对葡萄糖合成的需求，因此节省了其前体，肌肉来源的氨基酸。正常70公斤。人在饥饿中存活2-3个月而不是几周，肥胖的人存活数月到一年以上。如果没有这种代谢适应，H.智人不可能进化出这么大的大脑。最近的研究表明，D-β-羟基丁酸，主要的“酮”，不仅是一种燃料，而且是一种比葡萄糖或脂肪酸更有效地产生ATP能量的“超级燃料”。在灌注大鼠心脏制备中，它增加了收缩力并降低了耗氧量。它还保护组织培养中的神经元细胞免受与阿尔茨海默氏症或帕金森氏症相关的毒素的影响。在啮齿动物模型中，它减少了失血性休克诱导的肺细胞死亡。此外，暴露于缺氧的小鼠存活时间更长。这些和其他数据表明，β-羟基丁酸酯在许多医疗和非医疗条件下的潜在用途，其中氧气供应或底物利用可能受到限制。正在努力制备可口服或胃肠外服用的β-羟基丁酸酯，以研究其潜在的治疗应用。
D-beta-hydroxybutyrate, the principal "ketone" body in starving man, displaces glucose as the predominating fuel for brain, decreasing the need for glucose synthesis in liver (and kidney) and accordingly spares its precursor, muscle-derived amino acids. Thus normal 70 kg. man survives 2-3 months of starvation instead of several weeks, and obese man many months to over a year. Without this metabolic adaptation, H. sapiens could not have evolved such a large brain. Recent studies have shown that D-beta-hydroxybutyrate, the principal "ketone", is not just a fuel, but a "superfuel" more efficiently producing ATP energy than glucose or fatty acid. In a perfused rat heart preparation, it increased contractility and decreased oxygen consumption. It has also protected neuronal cells in tissue culture against exposure to toxins associated with Alzheimer's or Parkinson's. In a rodent model it decreased the death of lung cells induced by hemorrhagic shock. Also, mice exposed to hypoxia survived longer. These and other data suggest a potential use of beta-hydroxybutyrate in a number of medical and non-medical conditions where oxygen supply or substrate utilization may be limited. Efforts are underway to prepare esters of beta-hydroxybutyrate which can be taken orally or parenterally to study its potential therapeutic applications.